Danlos FX, Grajeda-Iglesias C, Durand S, Sauvat A, Roumier M, Cantin D, Colomba E, Rohmer J, Pommeret F, Baciarello G, Willekens C, Vasse M, Griscelli F, Fahrner JE, Goubet AG, Dubuisson A, Derosa L, Nirmalathasan N, Bredel D, Mouraud S, Pradon C, Stoclin A, Rozenberg F, Duchemin J, Jourdi G, Ellouze S, Levavasseur F, Albigès L, Soria JC, Barlesi F, Solary E, André F, Pène F, Ackerman F, Mouthon L, Zitvogel L, Marabelle A, Michot JM, Fontenay M, Kroemer G
Cell Death Dis 12 (3) 258 [2021-03-11; online 2021-03-11]
The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient's plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.